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https://www.readbyqxmd.com/read/29913090/oral-chemotherapy-for-the-treatment-of-hepatocellular-carcinoma
#1
Shun Yamamoto, Shunsuke Kondo
Many clinical trials have been conducted with chemotherapies in patients with advanced hepatocellular carcinoma (HCC). However, few agents have shown efficacy. It is thought that the efficacy of some agents might have resulted from the heterogeneity of tumors, insufficient dosages due to liver cirrhosis, and post-therapy effects. In recent years, immune checkpoint inhibitors have shown promising clinical activity and safety in patients with advanced HCC. Areas covered: The authors provide an overview of chemotherapies used for the treatment of HCC, including ongoing trials...
June 18, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29912871/ar-negative-triple-negative-or-quadruple-negative-breast-cancers-in-african-american-women-have-an-enriched-basal-and-immune-signature
#2
Melissa Davis, Shweta Tripathi, Raymond Hughley, Qinghua He, Sejong Bae, Balasubramanyam Karanam, Rachel Martini, Lisa Newman, Windy Colomb, William Grizzle, Clayton Yates
There is increasing evidence that Androgen Receptor (AR) expression has prognostic usefulness in Triple negative breast cancer (TNBC), where tumors that lack AR expression are considered "Quadruple negative" Breast Cancers ("QNBC"). However, a comprehensive analysis of AR expression within all breast cancer subtypes or stratified by race has not been reported. We assessed AR mRNA expression in 925 tumors from The Cancer Genome Atlas (TCGA), and 136 tumors in 2 confirmation sets. AR protein expression was determined by immunohistochemistry in 197 tumors from a multi-institutional cohort, for a total of 1258 patients analyzed...
2018: PloS One
https://www.readbyqxmd.com/read/29912605/graft-rejection-after-immune-checkpoint-inhibitor-therapy-in-solid-organ-transplant-recipients
#3
Tor Magnus Smedman, Pål-Dag Line, Tormod K Guren, Svein Dueland
No abstract text is available yet for this article.
June 18, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29912415/primary-melanoma-histologic-subtype-impact-on-survival-and-response-to-therapy
#4
Michael Lattanzi, Yesung Lee, Danny Simpson, Una Moran, Farbod Darvishian, Randie H Kim, Eva Hernando, David Polsky, Doug Hanniford, Richard Shapiro, Russell Berman, Anna C Pavlick, Melissa A Wilson, Tomas Kirchhoff, Jeffrey S Weber, Judy Zhong, Iman Osman
Background: Two primary histologic subtypes, superficial spreading melanoma (SSM) and nodular melanoma (NM), comprise the majority of all cutaneous melanomas. NM is associated with worse outcomes, which have been attributed to increased thickness at presentation, and it is widely expected that NM and SSM would exhibit similar behavior once metastasized. Herein, we tested the hypothesis that primary histologic subtype is an independent predictor of survival and may impact response to treatment in the metastatic setting...
June 15, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29912044/cardiac-immune-related-adverse-events-in-immune-checkpoint-inhibition-therapy
#5
Aaron D Brumbaugh, Roshni Narurkar, Kaushal Parikh, Michael Fanucchi, William H Frishman
Immune checkpoint inhibitors present clinicians with both an exciting step forward in cancer treatment and the unknown possibilities of an unshackled immune system. The latter phenomena, known as immune-related adverse events (irAEs), are of particular interest because they may affect any organ system with autoimmune-like pathologies, such as hepatitis and colitis. Within the cardiovascular system, irAEs associated with immune checkpoint blockade exist as a broad clinical spectrum, with autoimmune myocarditis being the best-characterized entity at this time...
June 14, 2018: Cardiology in Review
https://www.readbyqxmd.com/read/29910814/the-role-of-natural-killer-group-2-member-d-in-chronic-inflammation-and-autoimmunity
#6
REVIEW
Marina Babic, Chiara Romagnani
Current medicine and medical science puts great effort into elucidating the basis of chronicity and finding appropriate treatments for inflammatory diseases; however, the mechanisms driving aberrant immune responses are mostly unknown and deserve further study. Of particular interest is the identification of checkpoints that regulate the function and differentiation of pro-inflammatory cells during pathogenesis, along with means of their modulation for therapeutic purposes. Natural killer group 2, member D (NKG2D) is a potent activator of the immune system, known as a sensor for "induced-self" ligands, i...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29910800/further-advances-in-cancer-immunotherapy-going-beyond-checkpoint-blockade
#7
REVIEW
Robert W Wilkinson, Andrew J Leishman
Significant advances have been made to identify effective therapies that either restore or generate de novo a patient's immune response to cancer, so-called immunotherapy or immuno-oncology (IO) therapies. Some tumors overcome immune surveillance by promoting mechanisms to evade or suppress the immune system. This conference report highlights the clinical promise and current challenges of IO therapy, including the use of immune-checkpoint antagonist monoclonal antibodies. Furthermore, this report investigates advances in preclinical modeling of cancer immunobiology and how this is helping our understanding of which patients will receive clinical benefits from current immune-checkpoint treatment...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29910728/regulation-of-pd-l1-emerging-routes-for-targeting-tumor-immune-evasion
#8
REVIEW
Yiting Wang, Huanbin Wang, Han Yao, Chushu Li, Jing-Yuan Fang, Jie Xu
Immune checkpoint blockade therapies (ICBTs) targeting programmed cell death 1 (PD-1) and its ligand programmed death ligand-1 (PD-L1/B7-H1/CD274) have exhibited momentous clinical benefits and durable responses in multiple tumor types. However, primary resistance is found in considerable number of cancer patients, and most responders eventually develop acquired resistance to ICBT. To tackle these challenges, it is essential to understand how PD-L1 is controlled by cancer cells to evade immune surveillance...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29909921/myositis-as-an-adverse-event-of-immune-checkpoint-blockade-for-cancer-therapy
#9
Mohsin Shah, Jean H Tayar, Noha Abdel-Wahab, Maria E Suarez-Almazor
OBJECTIVES: Immune checkpoint inhibitors (ICIs) can successfully treat cancer, but their use can be hindered by serious immune-related adverse events. We report six patients receiving ICIs who presented with de novo myositis. METHODS: We identified patients with myositis who were receiving ICIs between January 2004 and September 2016 at The University of Texas MD Anderson Cancer Center. RESULTS: Six patients developed de novo myositis. The mean age was 64...
May 18, 2018: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/29909499/immune-checkpoint-inhibitors-and-radiosurgery-for-newly-diagnosed-melanoma-brain-metastases
#10
Tyler P Robin, Robert E Breeze, Derek E Smith, Chad G Rusthoven, Karl D Lewis, Rene Gonzalez, Amanda Brill, Robin Saiki, Kelly Stuhr, Laurie E Gaspar, Sana D Karam, David Raben, Brian D Kavanagh, Sameer K Nath, Arthur K Liu
INTRODUCTION: Brain metastases are common in metastatic melanoma and radiosurgery is often utilized for local control. Immune checkpoint inhibitors (CPIs) play a central role in contemporary melanoma management; however, there is limited data exploring outcomes and potential toxicities for patients treated with CPIs and radiosurgery. METHODS: We retrospectively identified all consecutive cases of newly diagnosed melanoma brain metastases (MBM) treated with Gamma Knife radiosurgery at a single institution between 2012 and 2017, and included only patients that initiated CPIs within 8 weeks before or after radiosurgery...
June 16, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29908544/scrutinizing-the-expression-and-blockade-of-inhibitory-molecules-expressed-on-t-cells-from-acute-myeloid-leukemia-patients
#11
Mohsen Abdolmaleki, Nazanin Mojtabavi, Mahdi Zavvar, Mohammad Vaezi, Farshid Noorbakhsh, Mohammad Hossein Nicknam
T cell exhaustion is an immunosuppressive mechanism which occurs in chronic viral infections, solid tumors and hematologic malignancies. Exhausted T cell has increased the expression of inhibitory receptors, and functional impairment. In this study, we investigated the expression from some of those inhibitory receptors being Programmed death 1 (PD-1), T cell immunoglobulin and mucin domain containing molecules 3 (TIM-3) and CD244 on T cells from Iranian acute myeloid leukemia (AML) patients. Peripheral blood samples were collected from Iranian newly diagnosed AML patients and flow cytometric analysis was accomplished for cell surface expression of PD-1, TIM-3, and CD244 on T lymphocytes...
June 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29908324/pd-1-blockade-with-nivolumab-in-patients-with-recurrent-malignant-pleural-mesothelioma
#12
Josine Quispel-Janssen, Vincent van der Noort, Jeltje F de Vries, Marion Zimmerman, Ferry Lalezari, Erik Thunnissen, Kim Monkhorst, Robert Schouten, Laurel Schunselaar, Maria Disselhorst, Houke Klomp, Koen Hartemink, Sjaak Burgers, Wieneke Buikhuisen, Paul Baas
BACKGROUND: Malignant Pleural Mesothelioma (MPM) has limited treatment options and a poor outcome. PD-1/PD-L1 checkpoint inhibitors have proven efficacious in several cancer types. Nivolumab is a fully humanized monoclonal antibody against PD-1 with a favorable toxicity profile. In MPM, the immune system is considered to play an important role. We therefore tested nivolumab in recurrent MPM. METHODS: In this single center trial, patients with MPM received nivolumab 3mg/kg i...
June 13, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29908076/diabetes-associated-with-immune-checkpoint-inhibition-presentation-and-management-challenges
#13
A Galligan, W Xu, S Fourlanos, A Nankervis, C Chiang, A M Mant, P Parente, D Rischin, B Krishnamurthy, S Sandhu, P G Colman
BACKGROUND: In recent years, immune checkpoint blockade has become a standard therapy for a wide range of cancers. Adverse events including endocrinopathies result from the induction of autoimmunity. CASE REPORT: We report a case series of nine individuals who presented with immunotherapy-induced type 1 diabetes between 2015-2017. DISCUSSION: Onset of diabetes occurred within 12 weeks of commencing therapy. Anti- GAD antibodies were present in six people...
June 16, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29907739/nanoscale-metal-organic-frameworks-enhance-radiotherapy-to-potentiate-checkpoint-blockade-immunotherapy
#14
Kaiyuan Ni, Guangxu Lan, Christina Chan, Bryan Quigley, Kuangda Lu, Theint Aung, Nining Guo, Patrick La Riviere, Ralph R Weichselbaum, Wenbin Lin
Checkpoint blockade immunotherapy enhances systemic antitumor immune response by targeting T cell inhibitory pathways; however, inadequate T cell infiltration has limited its anticancer efficacy. Radiotherapy (RT) has local immunomodulatory effects that can alter the microenvironment of irradiated tumors to synergize with immune checkpoint blockade. However, even with high doses of radiation, RT has rarely elicited systemic immune responses. Herein, we report the design of two porous Hf-based nanoscale metal-organic frameworks (nMOFs) as highly effective radioenhancers that significantly outperform HfO2 , a clinically investigated radioenhancer in vitro and in vivo...
June 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29907693/exosomes-shuttle-trex1-sensitive-ifn-stimulatory-dsdna-from-irradiated-cancer-cells-to-dendritic-cells
#15
Julie M Diamond, Claire Vanpouille-Box, Sheila Spada, Nils-Petter Rudqvist, Jessica Chapman, Beatrix Ueberheide, Karsten A Pilones, Yasmeen Sarfraz, Silvia C Formenti, Sandra Demaria
Radiotherapy (RT) used at immunogenic doses leads to accumulation of cytosolic double-stranded DNA (dsDNA) in cancer cells, which activates type I IFN (IFN-I) via the cGAS/STING pathway. Cancer cell-derived IFN-I is required to recruit BATF3-dependent dendritic cells (DCs) to poorly immunogenic tumors and trigger antitumor T-cell responses in combination with immune checkpoint blockade. We have previously demonstrated that the exonuclease TREX1 regulates radiation immunogenicity by degrading cytosolic dsDNA...
June 15, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29907623/unexpected-benefits-of-aging-for-favorable-responses-to-pd-1-blockade-in-melanoma
#16
Graham Pawelec
Immunosenescence might be expected to reduce the efficacy of checkpoint blockade, which depends on a functionally intact immune system. However, it seems that older melanoma patients may respond better to anti-PD1 treatment than younger patients, possibly due to their having fewer regulatory T-cells relative to CD8+ T-cells within tumour deposits.
June 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29907570/the-endoplasmic-reticulum-resident-e3-ubiquitin-ligase-hrd1-controls-a-critical-checkpoint-in-b-cell-development-in-mice
#17
Yi Yang, Sinyi Kong, Yana Zhang, Johanna Melo-Cardenas, Beixue Gao, Yusi Zhang, Donna D Zhang, Bin Zhang, JianXun Song, Edward Thorp, Kezhong Zhang, Jinping Zhang, Deyu Fang
Humoral immunity involves multiple checkpoints that occur duringin B-cell development, maturation, and activation. The pre--B-cell receptor (pre-BCR) is expressed following the productive recombination of the immunoglobulin heavy- chain gene, and. sSignalsing through the pre-BCR are is required for the differentiation of pre-B cells into immature B cells. However, the molecular mechanisms controlling the pre-BCR expression and signaling strength remain undefined. Herein, we probed the role of the endoplasmic reticulum-associated, stress-activated E3 ubiquitin ligase HMG-CoA reductase degradation 1 (Hrd1) in B-cell differentiation...
June 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29907163/cytokine-release-syndrome
#18
REVIEW
Alexander Shimabukuro-Vornhagen, Philipp Gödel, Marion Subklewe, Hans Joachim Stemmler, Hans Anton Schlößer, Max Schlaak, Matthias Kochanek, Boris Böll, Michael S von Bergwelt-Baildon
During the last decade the field of cancer immunotherapy has witnessed impressive progress. Highly effective immunotherapies such as immune checkpoint inhibition, and T-cell engaging therapies like bispecific T-cell engaging (BiTE) single-chain antibody constructs and chimeric antigen receptor (CAR) T cells have shown remarkable efficacy in clinical trials and some of these agents have already received regulatory approval. However, along with growing experience in the clinical application of these potent immunotherapeutic agents comes the increasing awareness of their inherent and potentially fatal adverse effects, most notably the cytokine release syndrome (CRS)...
June 15, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29906817/is-immune-checkpoint-inhibition-part-of-standard-therapy-for-stage-iii-non-small-cell-lung-cancer
#19
Jyoti D Patel, Steven J Chmura
No abstract text is available yet for this article.
June 15, 2018: Cancer
https://www.readbyqxmd.com/read/29906735/patterns-of-disease-control-and-survival-in-patients-with-melanoma-brain-metastases-undergoing-immune-checkpoint-blockade
#20
Laura Milsch, Anja Gesierich, Sophia Kreft, Elisabeth Livingstone, Lisa Zimmer, Matthias Goebeler, Dirk Schadendorf, Bastian Schilling
OBJECTIVES: Immune-checkpoint blockers (ICBs) significantly prolong overall survival (OS) in patients with advanced melanoma. Limited data are available on the efficacy and clinical benefit in patients with melanoma brain metastases (MBMs). The aim of this study was to determine whether ICB is active in an unselected cohort treated of patients with known brain metastases and if disease control correlates with the survival. METHODS: A total of 385 patients with metastatic malignant melanoma treated with ICB as monotherapy between 2005 and 2017 in two tertiary referral centres were included...
June 12, 2018: European Journal of Cancer
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